Adelman Emmalee R, Figueroa Maria E
Department of Human Genetics.
Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Curr Opin Hematol. 2021 Jan;28(1):57-63. doi: 10.1097/MOH.0000000000000622.
Our understanding of the effects of aging on human hematopoiesis has advanced significantly in recent years, yet the full ramifications of these findings are not fully understood. This review summarizes these findings and discusses their implication as they relate to malignant hematopoiesis.
With human aging there is an impaired immune response, loss of hematopoietic stem cell (HSC) function, increase in clonal hematopoiesis, and higher frequency of myeloid malignancies. Although murine models have implicated abnormalities in DNA damage repair, autophagy, metabolism, and epigenetics, studies in primary human specimens are more limited. The development of age-related clonal hematopoiesis and the risk associated with this is one of the major findings in the field of recent years. This is accompanied by changes in bone marrow stem and progenitor composition, changes in the epigenetic program of stem cells and an inflammatory milieu in the bone marrow. The precise consequences of these changes for the development of age-related malignancies are still unclear.
Advances in the field have begun to reveal the mechanisms driving human HSC loss of function with age. It will be critical to delineate between normal and malignant aging in order to better prevent age-associated myeloid malignancies.
近年来，我们对衰老对人类造血作用的理解有了显著进展，但这些发现的全部影响尚未完全明了。本综述总结了这些发现，并讨论了它们与恶性造血的关系。
随着人类衰老，免疫反应受损，造血干细胞（HSC）功能丧失，克隆性造血增加，髓系恶性肿瘤的发生率更高。尽管小鼠模型表明DNA损伤修复、自噬、代谢和表观遗传学存在异常，但对原代人类标本的研究较为有限。与年龄相关的克隆性造血的发展及其相关风险是近年来该领域的主要发现之一。这伴随着骨髓干细胞和祖细胞组成的变化、干细胞表观遗传程序的变化以及骨髓中的炎症环境。这些变化对与年龄相关的恶性肿瘤发展的确切影响仍不清楚。
该领域的进展已开始揭示随着年龄增长导致人类造血干细胞功能丧失的机制。区分正常衰老和恶性衰老对于更好地预防与年龄相关的髓系恶性肿瘤至关重要。
